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Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor

The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the severa...

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Autores principales: Guida, F., Luongo, L., Boccella, S., Giordano, M. E., Romano, R., Bellini, G., Manzo, I., Furiano, A., Rizzo, A., Imperatore, R., Iannotti, F. A., D’Aniello, E., Piscitelli, F., sca Rossi, F., Cristino, L., Di Marzo, V., de Novellis, V., Maione, S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428303/
https://www.ncbi.nlm.nih.gov/pubmed/28336953
http://dx.doi.org/10.1038/s41598-017-00342-1
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author Guida, F.
Luongo, L.
Boccella, S.
Giordano, M. E.
Romano, R.
Bellini, G.
Manzo, I.
Furiano, A.
Rizzo, A.
Imperatore, R.
Iannotti, F. A.
D’Aniello, E.
Piscitelli, F.
sca Rossi, F.
Cristino, L.
Di Marzo, V.
de Novellis, V.
Maione, S.
author_facet Guida, F.
Luongo, L.
Boccella, S.
Giordano, M. E.
Romano, R.
Bellini, G.
Manzo, I.
Furiano, A.
Rizzo, A.
Imperatore, R.
Iannotti, F. A.
D’Aniello, E.
Piscitelli, F.
sca Rossi, F.
Cristino, L.
Di Marzo, V.
de Novellis, V.
Maione, S.
author_sort Guida, F.
collection PubMed
description The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation. This novel gene regulation mechanism was demonstrated through: (i) pharmacological PPAR-α manipulation, (ii) PPAR-α mRNA silencing, (iii) chromatin immunoprecipitation. Moreover, exposure to PEA induced morphological changes associated with a reactive microglial phenotype, including increased phagocytosis and migratory activity. Our findings suggest indirect regulation of microglial CB2R expression as a new possible mechanism underlying the effects of PEA. PEA can be explored as a useful tool for preventing/treating the symptoms associated with neuroinflammation in CNS disorders.
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spelling pubmed-54283032017-05-15 Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor Guida, F. Luongo, L. Boccella, S. Giordano, M. E. Romano, R. Bellini, G. Manzo, I. Furiano, A. Rizzo, A. Imperatore, R. Iannotti, F. A. D’Aniello, E. Piscitelli, F. sca Rossi, F. Cristino, L. Di Marzo, V. de Novellis, V. Maione, S. Sci Rep Article The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation. This novel gene regulation mechanism was demonstrated through: (i) pharmacological PPAR-α manipulation, (ii) PPAR-α mRNA silencing, (iii) chromatin immunoprecipitation. Moreover, exposure to PEA induced morphological changes associated with a reactive microglial phenotype, including increased phagocytosis and migratory activity. Our findings suggest indirect regulation of microglial CB2R expression as a new possible mechanism underlying the effects of PEA. PEA can be explored as a useful tool for preventing/treating the symptoms associated with neuroinflammation in CNS disorders. Nature Publishing Group UK 2017-03-23 /pmc/articles/PMC5428303/ /pubmed/28336953 http://dx.doi.org/10.1038/s41598-017-00342-1 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Guida, F.
Luongo, L.
Boccella, S.
Giordano, M. E.
Romano, R.
Bellini, G.
Manzo, I.
Furiano, A.
Rizzo, A.
Imperatore, R.
Iannotti, F. A.
D’Aniello, E.
Piscitelli, F.
sca Rossi, F.
Cristino, L.
Di Marzo, V.
de Novellis, V.
Maione, S.
Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_full Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_fullStr Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_full_unstemmed Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_short Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_sort palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the cb2 receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428303/
https://www.ncbi.nlm.nih.gov/pubmed/28336953
http://dx.doi.org/10.1038/s41598-017-00342-1
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